- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03059888
Trial of Orencia in Patients With Myasthenia Gravis
November 20, 2019 updated by: Johns Hopkins University
Pilot Trial of Orencia in Myasthenia Gravis Patients Inadequately Responsive to Conventional Immunotherapy
This pilot research study is being done to see if the drug abatacept (Orencia ®) will be helpful in treating patients with myasthenia gravis (MG) who do not respond satisfactorily to other drugs that are used to suppress the immune system.
Abatacept has been successful in treating experimental MG in laboratory animals, and this study is to determine its effectiveness in patients with MG.
Study Overview
Study Type
Interventional
Enrollment (Actual)
6
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 85 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Able to comprehend and willing to sign an Informed Consent Form (ICF)
- Male or female 16 to 85 years of age
- Diagnosis of DEFINITE Myasthenia Gravis
- History of inadequate response to conventional MG treatment
- Clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
- Female patients of childbearing potential who are not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and are using contraceptive drugs or devices to prevent pregnancy during their participation in the study
- Willing to cooperate with study requirements, including visits to the study site every 2 months.
Exclusion Criteria:
- Subject's MG is responding adequately to conventional immunosuppressive treatment
- Subject has had no previous trial of other immunosuppressive agents
- Subject has a history of Chronic Obstructive Pulmonary Disease (COPD)
- Subject is impaired, incapacitated or incapable of completing study-related assessments
- Subject has the presence at screening of any severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic or cerebral disease, whether or not related to MG that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in the study.
- Female subject has a history of breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded by additional clinical, laboratory or other diagnostic evaluations
- Subject has a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
- Subject currently abuses drugs or alcohol
- Subject has evidence of active or latent bacterial or viral infections, including positive infectious disease laboratory test result (Hepatitis B, Hepatitis C or HIV)
- Subject has history of herpes zoster or cytomegalovirus (CMV) infection that resolved less than 2 months prior to screening visit
- Subject has received any live vaccine within 3 months of screening
- Subject has a history of serious bacterial infection within in the last 3 months, unless treated and resolved with antibiotics; or, any chronic bacterial infection
- Subject is at risk for tuberculosis
- Subject has any of the following laboratory values: Hemoglobin < 8.5 g/dL; White Blood Cells (WBC) < 3000 mm3; Platelets < 100,000 mm3; Serum creatinine > 2x upper limit of normal (ULN); Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2x ULN
- Subject is unable or unwilling to maintain weekly injection schedule
- Subject has undergone a change in immunosuppressive medications within the last three months prior to enrollment.
- Subject has neurological impairment due to a condition other than MG, including history of transient ischemic attack within the past year
- Subject has taken any investigational study drug within 28 days or five half-lives of the prior agent, whichever is greater, prior to dosing
- Subject has had previous exposure to Orencia (abatacept)
- Subject is a prisoner or is involuntarily incarcerated
- Subject is compulsorily detained for treatment of either psychiatric or physical illness
- Subject is judged to be actively suicidal or a suicide risk by the Investigator
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Abatacept
125mg abatacept in 1ml solution administered once per week by subcutaneous injection
|
Subcutaneous administration of abatacept
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subjective Composite Score of Myasthenia Gravis (MG) Severity
Time Frame: 12 months
|
The "Subjective Score of MG Severity" is a composite score of subjective measurements of MG severity as designed by Dr. Daniel Drachman.
The investigator will rate each subjective measure on a scale of 0 (no impairment) to 3 (severe impairment).
The composite score of these measurements determined at baseline and at two-month increments through 12 months.
The domains that make up the subjective score are: Diplopia, Ptosis, Arm strength, Leg strength, Speech, Voice, Chewing, Swallowing, Respiration, and General Health Status.
The change in the composite subjective score at 12 months as compared to baseline is one of the primary outcomes.
Patients that show an improvement in MG symptoms should have a lower score at 12 months as compared to baseline.
|
12 months
|
Objective Composite Score of Myasthenia Gravis (MG) Severity
Time Frame: 12 months
|
The "Objective Score of MG Severity" is a composite score of subjective measurements of MG severity as designed by Dr. Daniel Drachman.
The investigator will score each objective measure on a scale of 0 (no impairment) to 3 (severe impairment).
The composite score of these measurements determined at baseline and at two-month increments through 12 months.
The domains that make up the objective score are: Diplopia, Ptosis, Arm abduction, Gait, Orbicularis Oculi, Orbicularis Oris, Tongue, Slurp Test.
The change in the composite objective score at 12 months as compared to baseline is one of the primary outcomes.
Patients that show an improvement in MG symptoms should have a lower score at 12 months as compared to baseline.
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12 months
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Muscle Strength (Dynamometry)
Time Frame: 12 months
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Muscle strength in 11 muscle groups will be measured by hand-held dynamometry at baseline and at two-month increments through 12 months.
The change in muscle strength (in pounds) at 12 months as compared to baseline is one of the primary outcomes.
Patients that show an improvement in MG symptoms should show increased muscle strength at 12 months as compared to baseline.
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12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Myasthenia Gravis Composite Score (MGC)
Time Frame: 12 months
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The Myasthenia Gravis Composite (MGC) scale consists of test items that measure symptoms and signs of MG, with weighted response options.
The domains included in the MGC are: Ptosis, Double vision, Eye closure, Talking, Chewing, Swallowing, Breathing, Neck strength, Shoulder abduction and Hip flexion.
Each domain is rated by the Investigator on a weighted scale between 0 (no impairment) and 6 (severe impairment).
Patients that show an improvement in MG symptoms should have a lower score at 12 months as compared to baseline.
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12 months
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Myasthenia Gravis Quality of Life-15 (MG QOL15) Score
Time Frame: 12 months
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The MG-QOL15 is a brief survey, completed by the patient, that is designed to assess some aspects of "quality of life" related to myasthenia gravis.
Patients are given 15 statements that relate to their quality of life and are asked to chose how often that statement applies to them (Not At All, A Little Bit, Some-what, Quite A Bit, Very Much).
Their answers are assigned a score from 0 (not at all) to 4 (Very Much).
Patients that show an improvement in quality of life as related to their MG symptoms should have a lower score at 12 months as compared to baseline.
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12 months
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Acetylcholine Receptor (AChR) or Muscle-Specific Kinase (MuSK) Antibody Concentrations
Time Frame: 12 months
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For patients with positive AChR or MuSK antibody tests, the change in antibody concentration will be a secondary outcome.
Patients with MG will only be positive for one of these antibodies.
Improvement is often seen with reduction in titer of > 50%, therefore patients that show an improvement in MG symptoms should show a reduction in antibody levels at 12 months as compared to baseline.
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12 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Daniel Drachman, MD, Johns Hopkins University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 12, 2017
Primary Completion (Actual)
July 15, 2019
Study Completion (Actual)
July 15, 2019
Study Registration Dates
First Submitted
February 17, 2017
First Submitted That Met QC Criteria
February 17, 2017
First Posted (Actual)
February 23, 2017
Study Record Updates
Last Update Posted (Actual)
November 22, 2019
Last Update Submitted That Met QC Criteria
November 20, 2019
Last Verified
November 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms
- Autoimmune Diseases of the Nervous System
- Autoimmune Diseases
- Neoplasms by Site
- Neurologic Manifestations
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Nervous System Neoplasms
- Paraneoplastic Syndromes, Nervous System
- Paraneoplastic Syndromes
- Neuromuscular Junction Diseases
- Muscle Weakness
- Myasthenia Gravis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Abatacept
Other Study ID Numbers
- IRB00100059
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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